Current chemotherapy protocols for treatment of embryonal brain tumors in children may recommend administration of intrathecal chemotherapy, either by a lumbar tap or via an Ommaya reservoir. Children with concurrent hydrocephalus and shunts may have subtherapeutic levels of chemotherapy in the CSF due to constant CSF drainage to extra-CNS compartments. We present our experience in delivery of chemotherapy to children via programmable valves. A retrospective analysis of children with CNS malignancies together with hydrocephalus treated with a shunt and a programmable valve (CERTAS™ Plus Programmable Valves—Integra Life Sciences, proGAV®—Miethke) was conducted. Eighteen children up to 16 years of age (mean age 5 years) were included. Main pathologies included medulloblastomas (7) and atypical rhabdoid teratoid tumor (5). Each patient underwent 3–55 intrathecal injections (17 ± 14). One patient developed symptomatic hydrocephalus during the injection, which resolved with valve resetting. There were no infections, leaks, or major complications. One child required a wound revision due to exposure of the proximal catheter related to extremely thin skin. One patient experienced a “stuck” setting of the valve. Eight children are alive with no active disease, 25–80 months after shunt placement (52 ± 21). There were no late effects related to IT chemotherapy. Programmable ventriculoperitoneal valves are a safe method for delivery of intra-ventricular chemotherapy in children. This technique may potentially have an added value for children with concurrent shunts and may also obviate the need for an additional ventricular access device (such as an Ommaya reservoir).

This study aims to analyze the demographics, therapeutic approaches, and outcomes of pediatric sarcomas of the head and neck treated at a single tertiary referral center. We retrospectively reviewed the medical charts of all pediatric patients diagnosed with head and neck sarcomas treated at the Tel Aviv Sourasky Medical Center during 2002–2021. Clinical data, oncologic and surgical treatments, and outcome measures were retrieved from electronic medical files. A total of 52 patients met the inclusion criteria. The mean age at diagnosis was 7.25 ± 6.04 years (range 2 months to 20 years), and the male-to-female ratio was 1.4: 1. The leading histological subtypes were rhabdomyosarcoma (RMS) (50

BACKGROUND:Weight loss and malnutrition are common findings in pediatric oncology patients, but their prognostic significance is controversial. We sought to evaluate the correlation between weight loss and response to neo-adjuvant chemotherapy in pediatric patients with osteosarcoma.PROCEDURE:All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between January 2011 and October 2022 were retrospectively reviewed.RESULTS:Sixty-three patients were suitable for study inclusion. Data on changes in their body weight between the initiation of neo-adjuvant chemotherapy and local therapy (tumor resection) were extracted. Response to chemotherapy was assessed by the percentage of tumor necrosis at the time of surgery. There was a significant direct correlation between a weight loss of 3% and above and good response to chemotherapy as demonstrated by tumor necrosis above 90%.CONCLUSIONS:Low caloric intake may imitate a caloric restriction diet that was proven to improve response to therapy in some oncological diseases. Further prospective trials are needed for the establishment of recommended caloric intake during chemotherapy in pediatric patients with osteosarcoma.

BACKGROUND:Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity. OBJECTIVE:To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel. METHODS:We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild-type ELANE/G6PC3 were referred for next-generation sequencing. RESULTS:Sixty-five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman-Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte-colony stimulating factor or due to myeloid transformation. CONCLUSIONS:The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow-up.

Curettage with or without the use of adjuvants is the standard of care in the treatment of an aneurysmal bone cyst (ABC). Historically, our approach combined curettage, high-speed burr drilling, and cryoablation. However, treatments varied based on age, tumor location, and surgeon preference. We asked: (1) Does cryoablation in addition to curettage and burr drilling decrease the local recurrence rates? (2) Are there any risk factors for the local recurrence rate? (3) Does cryoablation improve postsurgical functional outcomes in these patients? Patients treated for an ABC, between January 2006 and December 2019 were included in this retrospective analysis. Patient and surgical characteristics, such as age, gender, tumor location, type of treatment, time of follow-up, recurrence rate, and functional outcome measured by the Musculoskeletal Tumor Society Score 1993 (MSTS93) score were compared between those treated with and without cryoablation. Both groups, without cryoablation (n = 88) and with cryoablation (n = 42), showed no significant difference in local recurrence rates (9.1% vs. 7.1%, p = 0.553) and functional outcomes as measured by the MSTS93 score (28.9 vs. 27.8, p = 0.262). Risk factors analyzed did not significantly affect local recurrence risk, except for secondary ABC diagnosis (p = 0.017). The cryoablation group had a more extended follow-up (45.6 vs. 73.2 months, p < 0.001), reflecting a shift in practice over time. We found no significant difference in local recurrence rate or functional outcome in patients treated with or without cryoablation. Formal curettage with additional high-speed burr drilling provides effective tumor control and favorable functional outcomes, negating the need for adjuvant cryoablation.

PurposeNoonan syndrome (NS) is a rare neurodevelopmental syndrome characterized by dysmorphic features, congenital heart defects, neurodevelopmental delay, and bleeding diathesis. Though rare, several neurosurgical manifestations have been associated with NS, such as Chiari malformation (CM-I), syringomyelia, brain tumors, moyamoya, and craniosynostosis. We describe our experience in treating children with NS and various neurosurgical conditions, and review the current literature on neurosurgical aspects of NS.MethodsData were retrospectively collected from the medical records of children with NS who were operated at a tertiary pediatric neurosurgery department, between 2014 and 2021. Inclusion criteria were clinical or genetic diagnosis of NS, age < 18 years at treatment, and need for a neurosurgical intervention of any kind.ResultsFive cases fulfilled the inclusion criteria. Two had tumors, one underwent surgical resection. Three had CM-I, syringomyelia, and hydrocephalus, of whom one also had craniosynostosis. Comorbidities included pulmonary stenosis in two patients and hypertrophic cardiomyopathy in one. Three patients had bleeding diathesis, two of them with abnormal coagulation tests. Four patients were treated preoperatively with tranexamic acid, and two with Von Willebrand factor or platelets (1 each). One patient with a clinical bleeding predisposition developed hematomyelia following a syringe-subarachnoid shunt revision.ConclusionsNS is associated with a spectrum of central nervous system abnormalities, some of which with known etiology, while in others a pathophysiological mechanism has been suggested in the literature. When operating on a child with NS, a meticulous anesthetic, hematologic, and cardiac evaluation should be conducted. Neurosurgical interventions should then be planned accordingly.

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%-80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescence. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared with those with local disease. High NET formation at diagnosis predicted poor response to neoadjuvant chemotherapy, relapse, and death from disease (p < 0.05). NET formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared with pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NET formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

To the Editor: Ewing sarcoma (ES) is an aggressive neoplasm that typically affects adolescents and young adults.1,2 The need for integration of systemic and local treatments for ES treatment is well accepted.3 The prognosis of patients with ES refractory to first-line treatment or who sustain recurrence during therapy is poor, with a 3-year event-free survival (EFS) rate of less than 30%.4 The CABONE study showed some efficacy with the use of cabozantinib in heavily pretreated ES patients.5 We present a report on successful curative-intent cabozantinib treatment of a patient with chemo-refractory disease. A 19-year-old male presented with pain and swelling of his right shin. A positron emission tomography (PET)-computed tomography (CT) demonstrated pathologic fluorodeoxyglucose (FDG) uptake in the right fibula (Figure 1C). A magnetic resonance imaging (MRI) study showed an extension of the large enhancing soft-tissue component to involve the popliteal neurovascular bundle (Figure 2). Two small lesions were also demonstrated in the proximal tibia. A biopsy from the fibula confirmed the diagnosis of ES. Chemotherapy was initiated according to the AEWS0031 protocol.6 The MRI findings following four cycles of chemotherapy showed no change in size or enhancement of themass in the fibula and tibia, and a suspected new lesion in the medial tibia. A biopsy taken from the tibia lesions showed viable disease with no signs of necrosis, leading to a diagnosis of refractory progressive disease. At that point, it was decided to use radiation for local control and to switch the chemotherapy to irinotecan and temodal. The patient received radiation therapy consisting of 60 Gy to the fibula and tibia lesions. He developed severe abdominal pain and diarrhea following the first cycle of chemotherapy, leading to change of treatment to topotecan, cytoxan, and vincristine. No change in FDG uptake was demonstrated onPET-CT following three chemotherapy cycles in combination with local irradiation. It was decided to start treatment with cabozantinib at a dose of 60 mg once daily. Clinical improvement was evident 1 month later. An MRI performed 6 weeks since the initiation of cabozantinib treatment demonstrated a reduction in tumor size togetherwith tumorenhancement regression (Figure2B). Fourmonths later, he underwent complete wide margins tumor resection of the proximal fibula, debridement, and curettage of the tibial lesions. The peroneal nerve was resected and reconstructed by a sural nerve graft. The pathology examination demonstrated 90% necrosis with clean marginsof theprimary tumor in the fibula, andno tumor cellswithin the tibial lesions. The patient is currently in complete remission at 1 year from the initiation of cabozantinib treatment. ES is an aggressive bone and soft-tissue tumor. Treatment includes induction chemotherapy, followed by local therapy and adjuvant chemotherapy. We used the AEWS0031 protocol that had demonstrated a 5-year EFS of 73% in patients receiving the dose-intensified schedule.6 There is no standard approach for the treatment of patients who do not respond to thatmanagement, orwho experience relapse. There are several chemotherapy regimens, which have demonstrated responses to therapy in this setting; however, the superiority of one regimen over another has not yet been established.7 Tyrosine kinase inhibitors have recently become an option in relapse-refractory ES. The expression of MET tyrosine kinase in solid tumors was shown to be correlated with poor overall survival.8 The first study to implicate MET in ES demonstrated, that MET is ubiquitously expressed in ES, mostly cytoplasmic, and that MET inhibitors affected ES cell viability in vitro.9 The first trial assessing the activity of cabozantinib in ES was a multicenter, phase 2 trial.5 All of the recruited patients had documented disease progression, and all were treated with cabozantinib at a dose of 60 mg/m2 for adults and 40 mg/m2 for adolescents. An objective response (all partial) was demonstrated in 26% of the ES patients. The potential of treating patients with ES was discussed in an opinion paper that summarized the use of cabozantinib in various oncological diseases.10 There are only two additional descriptions of cabozantinib treatment in patients with ES in the literature. One was a phase 1 trial that failed to define a maximal tolerated dose in pediatric patients with relapsed or refractory solid tumors.11 The other was a case report of an adult patient with refractory metastatic ES who first responded to cabozantinib but unfortunately suffered from disease progression 8 months after the initiation of therapy.12 After the initiation of cabozantinib in our patient, there was amajor clinical improvement followed by radiologic regression of his disease. The extent of tumor reduction enabled subsequent cleanmargin resection of the tumor. Disease responsewas evident by 90%necrosis of the tumor cells on resection. This is a description of cabozantinib as a successful salvage regimen in chemo-refractory ES. The unexpectedly good response to therapy raises the possibility of adding this therapy in cases resistant to currently first-line protocols. There is a need for further investigation

Abstract INTRODUCTION: Current chemotherapy protocols for treatment of embryonal brain tumors in infants recommend administration of intrathecal chemotherapy either by a lumbar tap or via an Ommaya reservoir. Children with concurrent hydrocephalus and shunts may have sub-therapeutic levels of chemotherapy in the CSF due to constant CSF drainage to extra-CNS compartments. We present our experience in delivery of chemotherapy to young children via programmable valves. RESULTS: A retrospective analysis of infants with CNS malignancies and hydrocephalus treated with a shunt and a programmable valve (CERTAS™ Plus Programmable Valves - Integra Life Sciences) was conducted. Five infants 1.1-3 years of age (mean 2) were included. Pathologies included atypical teratoid rhabdoid tumor (ATRT N=2), medulloblastoma (N=2), and metastatic rhabdomyosarcoma(N=1). Intrathecal injections were conducted in an outpatient setting unless hospitalization was required for other reasons. Only one child required sedation due to noncompliance. A total of 61 chemotherapeutic administrations were performed directly through the valve while set on an extremely high opening pressure for several hours( 35 with hydrocortisone and cytarabine, 26 with topotecan). There were no infections, leaks or major complications. One child required a wound revision due to exposure of the proximal catheter related to extremely thin skin, one child developed somnolence and fever which were not related to a shunt malfunction or infection, and one child had clinical and radiological shunt over-drainage solved by increasing of valve settings. CONCLUSIONS: Programmable ventriculoperitoneal valves appear to a safe method for delivery of chemotherapy in infants with malignant CNS tumors .This technique may potentially have an added value for children with concurrent shunts, and may also obviate the need for an additional ventricular access device .

Mucositis, a painful and debilitating condition, is a common side effect of chemotherapy. The role of tramadol in the treatment of mucositis in pediatric patients has not yet been determined. In this retrospective study, we evaluate whether tramadol as single agent achieved a reduction of pain intensity among oncologic children admitted for mucositis. In total, 34 of 54 (63%) episodes were treated with tramadol alone and achieved adequate pain relief. Tramadol's side effects were mild and manageable.

To determine the incidence, clinical presentation, and outcome of methotrexate (MTX) associated neurotoxicity in pediatric patients treated for osteosarcoma, with the aim of identifying possible risk factors and suggesting recommended treatment for these sequelae. All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between November 2011 and August 2021 were retrospectively reviewed. All patients were treated according to the EURAMOS AOST0331 protocol, using cisplatin, doxorubicin, and high-dose MTX at a dose of 12 g/m2 over 4 h. Seventy-eight patients with osteosarcoma were identified (age range 5 to 23 years, 42 males). Seven patients (9%) sustained neurotoxicity following treatment with high-dose MTX. Manifestations of neurotoxicity included among others, generalized seizures, confusion, encephalopathy, dysarthria, and choreiform movements. All but one episode occurred following two sequential cycles of high-dose MTX. All 7 had subacute toxicity, 5–10 days following MTX administration, and 1 had both acute and subacute toxicity. Brain MRI was performed for all patients and demonstrated typical MRI changes attributed to MTX neurotoxicity in 4 of them. Two patients received aminophylline; one patient received dextromethorphan. Patients with normal MRI imaging resumed MTX therapy without any sequels. No risk factors were found for high-dose MTX-related toxicity occurrence. The time of risk of neurotoxicity due to high-dose MTX treatment for osteosarcoma is days 5–10 following two sequential treatment cycles. These findings together with treatment options for these adverse effects should be detailed in the therapeutic protocol of MTX use among pediatric patients with osteosarcoma.

BACKGROUND:Infantile myofibromatosis (IM) is a rare benign fibrous tumor with diverse clinical presentations and treatments, such as watchful waiting, surgical excision, and low-dose chemotherapy.PROCEDURE:Clinical presentation and tailored treatment of five infants with solitary and generalized IM are described, together with a review of the literature.RESULTS:Three patients underwent total-body magnetic resonance imaging (MRI) at diagnosis and during follow up, which revealed disease extension that aided in designing treatment. Visceral involvement included central nervous system, cardiac, gastrointestinal, muscle, bone, and subcutaneous tissue lesions. The patient with the solitary form of IM was followed up without treatment and had spontaneous improvement. Patients with the multicentric form received intravenous low-dose methotrexate and vinblastine chemotherapy. One patient who received oral methotrexate due to cardiac involvement and unfeasible central line access had excellent results. Recurrence was successfully treated by the same methotrexate and vinblastine regimen as that administered at diagnosis.CONCLUSIONS:We suggest screening all patients with one or more IM lesions by means of total body MRI due to its inherent superior soft tissue resolution. Total-body MRI may also be used for routine follow up. Oral methotrexate can be administered successfully in patients that lack central line access, and recurrent lesions can be treated with the same chemotherapeutic combination as that given at diagnosis. Long-term follow up is needed, since recurrence could appear years after initial presentation of the disease.

Immune thrombocytopenic purpura (ITP) is a common cause of symptomatic thrombocytopenia in children, most of whom present with cutaneous and mucosal bleeding. Complications, such as intracranial hemorrhage and occult hemorrhage from various sites, are rare, and retinal hemorrhage is exceptionally rare. Our institutional clinical practice guidelines for managing ITP in the pediatric emergency department (PED) include routine funduscopy. The aim of this retrospective case series is to provide evidence-based recommendations for a tertiary care PED work-up of ITP, with special emphasis on the guidelines for funduscopy. The medical records of all pediatric patients diagnosed with ITP over a 4-year period (2013–2016) who had a platelet count < 50,000/mm3 were retrieved and reviewed. Seventy-five patients with thrombocytopenia (platelet count < 50,000/mm3) were diagnosed as having ITP in the PED. Sixty-one (79%) of these patients underwent funduscopy and retinal hemorrhage was ruled out in all of them, indicating that retinal hemorrhage as a complication of ITP is very rare.

OBJECTIVE:To present a rare case of "huge" hydronephrosis causing distortion of large vessels and formation of a thrombus in the inferior vena cava. Multidisciplinary treatment was applied with particular focus on pyeloplasty utilizing a robot-assisted laparoscopic approach.METHODS:A 20-month-old male presented to the emergency room severely ill with abdominal pain, nausea, vomiting, and fever and was subsequently transferred to the intensive care unit, in septic shock. An abdominal ultrasound revealed a large multilobular cystic structure in the right hemiabdomen, which was initially interpreted as an infected mesenteric cyst. CT scan revealed a huge hydronephrotic kidney crossing the midline, causing a mass effect that compressed and distorted the vena cava laterally, in addition to a thrombus between the hepatic vein and right renal vein. Intravenous Ceftriaxone and Amikacin, as well as anticoagulation therapy with low molecular weight heparin (Enoxaparin) were initiated. A nephrostomy tube was inserted that drained 900 mL of purulent urine. A full hematology investigation including protein C, S, and antithrombin III was carried out, excluding factor V Leiden and prothrombin mutation. All values were in the normal range. Dimercaptosuccinic Acid (DMSA) scan showed 30% function on the affected kidney and Voiding Cystourethrogram (VCUG) excluded any bladder pathology or reflux. Subcutaneous Enoxaparin was continued for 3 months, maintaining antifactor Xa in the therapeutic range (0.7-1 IU/mL). Ultrasound Doppler of the vena cava showed full resolution of the thrombus. Robot-assisted laparoscopic pyeloplasty was performed and significant reduction of the renal pelvis was carried out, taking care to preserve the calyces. Postoperative ultrasound 4 months after surgery showed a complete resolution of the hydronephrosis.CONCLUSION:Giant hydronephrosis is a rare finding. Distortion of adjacent veins and formation of thrombosis should be kept in mind, as they are life threatening. A multidisciplinary collaboration is mandatory to ensure optimal treatment.

Numerous adults' studies demonstrated that preaphaeresis CD34+ cells significantly correlate with the number of CD34+ cells collected by the aphaeresis procedure. Equivalent studies in children are scarce. We studied retrospectively 92 aphaeresis procedures performed following chemotherapy (44) or in steady state (48) in 60 pediatric patients (40 males, 20 females), median age of 7.5 years. Aphaeresis procedures were performed using a SPECTRA Optica (TERUMOBCT) continuous flow cell separator. CD34+ cell concentrations were assessed using flow cytometry. A highly significant correlation between peripheral CD34 cell count on the day of aphaeresis and CD34 cell yield per kg (R2 = .824, P < .0001) was demonstrated. A higher preaphaeresis CD34 cell count was demonstrated in patients with higher preaphaeresis white blood cell count, in patients with brain tumors, and in patients who received chemotherapy as part of their mobilization protocol. A threshold number of 20 peripheral CD34+ cell/μL was found to predict harvesting of 3 × 106 stem cells/kg, and 30 peripheral CD34+ cell/μL for harvesting of 5 × 106 stem cells/kg. This significant correlation between peripheral CD34 cell count and CD34 cell yield, and the threshold number of peripheral CD34 found to predict adequate harvesting can be useful in planning the optimal time for aphaeresis in children.

BACKGROUND:Immunocompromised patients exposed to varicella may experience significant morbidity and a 7% mortality rate. Management and outcome of an outbreak of varicella infection among hospitalized pediatric hemato-oncology patients using the guidelines of the American Academy of Pediatrics Committee on Infectious Diseases are presented.METHODS:This retrospective study describes an outbreak of varicella infection between February 2011 and June 2011. Data were retrieved from the patients' files. Positive polymerase chain reaction results for varicella zoster virus from vesicular skin lesions were used for the diagnosis of varicella infection.RESULTS:Twelve pediatric hemato-oncology patients experienced 13 episodes of varicella infection, 11 underwent 1 episode each and 1 patient had 2 episodes. All exposed patients without immunity received varicella zoster immune globulins or intravenous immunoglobulin and were isolated as recommended by the guidelines. Infected patients received intravenous acyclovir. One patient with acute lymphoblastic leukemia at induction chemotherapy died. All the other patients survived.CONCLUSIONS:Our experience in the management of hospitalized immunocompromised patients exposed to varicella was that a positive IgG serology did not confer protection after exposure to varicella infection and thus can not serve as a marker for immunity. Unlike the isolation period sufficient for immunocompetent patients, crusted lesions can be contagious and thus require extended isolation for immunocompromised patients. Patients receiving rituximab are at greater risk of having persistent or recurrent disease. Studies with a larger sample size should be performed to better assess the management of immunocompromized patients exposed to varicella.

Hyper-Eosinophilic Syndrome (HES) represents a heterogeneous group of conditions and can be either idiopathic or secondary to variety of underlying causes. We present a novel etiology for severe hypereosinophilia in a pediatric patient. An 8y/o boy presented with fever, gastrointestinal symptoms, worsening of background asthma and an absolute eosinophil count of ∼40,000. Screening for end-organ damage was negative and he was treated empirically for a possible helminth infection. The patient responded well to corticosteroids but eosinophil counts rose upon prednisone taper. Bone-marrow (BM) biopsy was normal except for significantly increased eosinophils. TCR repertoire and screening for associated genetic abnormalities (BCR-ABL1, FIP1L1-PDGFRA, PDGFRB rearrangement) was negative. Despite normal karyotype, cytogenetic studies were performed in search for chromosomal aberrations. FISH studies using probes to detect AML/ALL associated translocations, revealed a triple signal of the chromosome 21 probe in 20% of BM cells. The probe staining pattern, with close proximity of 2 of the 3 hybridization signals, suggested a partial duplication of chromosome 21. The percent of triple-21-probe cells did not correlate with 50% eosinophils in BM and FISH of skin fibroblasts or peripheral blood. Taken together, these findings support a somatic variation, possibly in a non-eosinophilic cell lineage. Interestingly, the probe used was complementary to RUNX1 (AML1), a transcription factor involved in differentiation of hematopoietic stem cells into myeloid and lymphoid lines. RUNX1 copy number variance might drive eosinophil proliferation and cytogenetic studies should be considered in the evaluation of HES.